Among non-critically ill patients with hypoxaemia who were admitted to hospital with coronavirus disease 2019 (COVID-19), a multifaceted intervention to increase prone positioning did not improve outcomes, according to a study published in The BMJ.
However, Michael Fralick, Sinai Health, Toronto, Canada, and colleagues noted that “wide confidence intervals preclude definitively ruling out benefit or harm,” and that “adherence to prone positioning was poor, despite multiple efforts to increase it.”
The multicentre randomised clinical trial conducted at 15 hospitals in Canada and the US from May 2020 until May 2021 involved patients who had a laboratory confirmed or a clinically highly suspected diagnosis of COVID-19, needed supplemental oxygen (up to 50% fraction of inspired oxygen), and were able to independently lie prone with verbal instruction. Of the 570 patients assessed for eligibility, 257 were randomised and 248 were included in the analysis. Patients were randomised to prone positioning (n = 126) or standard of care (n = 122).
The median age of patients was 56 (interquartile range [IQR] 45-65) years and the cohort comprised 89 (36%) female patients. At the time of randomisation, 222 (90%) patients were receiving oxygen via nasal prongs. The median time from hospital admission until randomisation was 1 day, while the median time spent prone in the first 72 hours was 6 (IQR 1.5-12.8) hours in total for the prone arm compared with 0 (IQR 0-2) hours in the standard of care arm.
The primary outcome was a composite of in-hospital death, mechanical ventilation, or worsening respiratory failure defined as needing at least 60% fraction of inspired oxygen for at least 24 hours. Secondary outcomes included the change in the ratio of oxygen saturation to fraction of inspired oxygen.
Overall, the risk of the primary outcome was similar between the prone group (18 [14%] events) and the standard of care group (17 [14%] events) (odds ratio 0.92, 95% confidence interval [CI] 0.44 to 1.92).
Further, researchers did a post hoc exploratory analysis and compared outcomes at the sites with the highest adherence to prone positioning against the sites with the lowest adherence. They found no difference in the primary outcome at the sites with the highest adherence; however, the researchers pointed out that the null finding “might be related to lack of statistical power because of the relatively low number of overall events or because the longer duration of prone positioning may still be insufficient for a clinically important benefit.”
The researchers also did a pre-planned subgroup analysis to identify how baseline hypoxaemia may affect the efficacy of prone positioning. In that analysis, they identified a lower risk of the primary outcome for patients randomised to prone positioning who needed 30% fraction of inspired oxygen or lower at the time of randomisation. Nonetheless, the researchers noted that “this should be considered hypothesis generating … because of the low overall number of events, which increases the possibility of chance alone underlying our observed findings,” adding that “future studies are needed to identify whether this finding is replicable and robust across other protocols.”
Meanwhile, the change in the ratio of oxygen saturation to fraction of inspired oxygen after 72 hours was similar for patients randomised to prone positioning and standard of care.
“In our multicentre pragmatic randomised clinical trial of encouraging prone positioning in patients admitted to hospital with COVID-19 who were hypoxaemic but not critically ill, we did not observe improvements in the risk of the composite of death, mechanical ventilation, or worsening respiratory failure. However, the wide confidence intervals preclude definitively ruling out benefit or harm. The trial was stopped early on the basis of the futility of finding the pre-specified effect size,” the researchers remarked.
The researchers further noted that “the poor adherence to prone positioning that [was] observed highlights that it is generally not well tolerated and innovative approaches are needed to improve adherence,” adding that “ongoing studies are evaluating whether prone positioning might be beneficial for non-intubated patients with more severe forms of hypoxaemia.”